Cell differentiation typically occurs with concomitant shape transitions to enable specialized functions. To adopt a different shape, cells need to change the mechanical properties of their surface. However, whether cell surface mechanics control the process of differentiation has been relatively unexplored. Here we show that membrane mechanics gate exit from naive pluripotency of mouse embryonic stem cells. By measuring membrane tension during early differentiation, we find that naive stem cells release their plasma membrane from the underlying actin cortex when transitioning to a primed state. By mechanically tethering the plasma membrane to the cortex by enhancing Ezrin activity or expressing a synthetic signaling-inert linker, we demonstrate that preventing this detachment forces stem cells to retain their naive pluripotent identity. We thus identify a decrease in membrane-to-cortex attachment as a new cell-intrinsic mechanism that is essential for stem cells to exit pluripotency.

细胞分化通常伴随形状转变发生以实现专门的功能。为了采用不同的形状，细胞需要改变其表面的机械性能。但是，细胞表面力学是否控制分化过程尚未得到充分的研究。在这里，我们显示膜力学门从小鼠胚胎干细胞的幼稚多能性退出。通过测量早期分化过程中的膜张力，我们发现，当转变为启动状态时，幼稚干细胞会从潜在的肌动蛋白皮质释放质膜。通过通过增强Ezrin活性或表达合成的信号惰性接头，将质膜机械地拴在皮层上，我们证明了防止这种分离会迫使干细胞保持其幼稚的多能性身份。